This trial is conducted globally. The aim of the trial is to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes. The trial is event-driven, i.e. the maximum trial duration (up to max. 148 weeks) will depend on the accrual of major adverse cardiovascular events (MACE) in this trial and the remaining research programme. The incidence of MACE will be monitored throughout the trial which will be terminated according to plan when pre-specified stopping criteria are met.

Time from randomisation to first occurrence of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke [ Time Frame: Time from randomisation up to end of follow-up (up to max. 148 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from randomisation to first occurrence of an expanded composite cardiovascular outcome [ Time Frame: Time from randomisation up to end of follow-up (up to max. 148 weeks) ] [ Designated as safety issue: No ]

Time from randomisation to each individual component of the expanded composite cardiovascular outcome [ Time Frame: Time from randomisation up to end of follow-up (up to max. 148 weeks) ] [ Designated as safety issue: No ]

Time from randomisation to first occurrence of all-cause death, non-fatal MI, or non-fatal stroke [ Time Frame: Time from randomisation up to end of follow-up (up to max. 148 weeks) ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: glycosylated haemoglobin (HbA1c) [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: fasting plasma glucose [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: body weight [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: lipid profile [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: urinary albumin to creatinine ratio [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: vital signs [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Incidence during the treatment period in other treatment outcomes: hypoglycaemic events [ Time Frame: Week 0 - 143 ] [ Designated as safety issue: No ]

Incidence during the treatment period in other treatment outcomes: adverse events [ Time Frame: Weeks 0-143 ] [ Designated as safety issue: No ]

Occurrence during the treatment period in other treatment outcomes: anti-semaglutide antibodies [ Time Frame: Weeks 0-143 ] [ Designated as safety issue: No ]

Change from baseline to last assessment during the treatment period in other treatment outcomes: patient reported outcome (PRO) [ Time Frame: Week 0, up to week 143 ] [ Designated as safety issue: No ]

Once weekly doses of 0.5 mg semaglutide after an initial dose escalation step of 0.25 mg as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)

Experimental: Semaglutide 1.0 mg

Drug: semaglutide

Once weekly doses of 1.0 mg semaglutide after an initial dose escalation step of 0.25 mg followed by 0.5 mg dose escalation as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)

Placebo Comparator: Semaglutide placebo 0.5 mg

Drug: placebo

Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment.

Administered subcutaneously (s.c., under the skin).

Placebo Comparator: Semaglutide placebo 1.0 mg

Drug: placebo

Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment.

Administered subcutaneously (s.c., under the skin).

Eligibility

Ages Eligible for Study:

50 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Men and women with type 2 diabetes mellitus

Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease or age above or equal to 60 years at screening and subclinical evidence of cardiovascular disease

Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs

HbA1c above or equal to 7.0% at screening

Exclusion Criteria:

Type 1 diabetes mellitus

Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening

Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening

Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness

Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening

History of chronic pancreatitis or idiopathic acute pancreatitis

Acute coronary or cerebro-vascular event within 90 days prior to randomisation

Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma

Personal history of non-familial medullary thyroid carcinoma

Screening calcitonin above or equal to 50 ng/L

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720446